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Introduction

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  • Central Neurons Receive Excitatory and Inhibitory Inputs

  • Excitatory and Inhibitory Synapses Have Distinctive Ultrastructures

  • Excitatory Synaptic Transmission Is Mediated by Ionotropic Glutamate Receptor-Channels That Are Permeable to Sodium and Potassium

    • The Excitatory Ionotropic Glutamate Receptors Are Encoded by a Distinct Gene Family

    • Glutamate Receptors Are Constructed from a Set of Modules

    • NMDA and AMPA Receptors Are Organized by a Network of Proteins at the Postsynaptic Density

  • Inhibitory Synaptic Action Is Usually Mediated by Ionotropic GABA and Glycine Receptor-Channels That Are Permeable to Chloride

    • Currents Through Single GABA and Glycine Receptor-Channels Can Be Recorded

    • Chloride Currents Through Inhibitory GABAA and Glycine Receptor-Channels Normally Inhibit the Postsynaptic Cell

  • Ionotropic Glutamate, GABA, and Glycine Receptors Are Transmembrane Proteins Encoded by Two Distinct Gene Families

    • Ionotropic GABAA and Glycine Receptors Are Homologous to Nicotinic ACh Receptors

    • Some Synaptic Actions Depend on Other Types of Ionotropic Receptors in the Central Nervous System

  • Excitatory and Inhibitory Synaptic Actions Are Integrated by the Cell into a Single Output

    • Synaptic Inputs Are Integrated to Fire an Action Potential at the Axon Initial Segment

    • Dendrites Are Electrically Excitable Structures That Can Fire Action Potentials

    • Synapses on a Central Neuron Are Grouped According to Physiological Function

  • An Overall View

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Like synaptic transmission at the neuromuscular junction, most rapid signaling between neurons in the central nervous system involves ionotropic receptors in the postsynaptic membrane. Thus, many principles that apply to the synaptic connection between the motor neuron and skeletal muscle fiber at the neuromuscular junction also apply in the central nervous system. Synaptic transmission between central neurons is more complex, however, for several reasons. First, although most muscle fibers are innervated by only one motor neuron, a central nerve cell (such as the motor neuron in the spinal cord) receives connections from hundreds or even thousands of neurons. Second, muscle fibers receive only excitatory inputs, whereas central neurons receive both excitatory and inhibitory inputs. Third, all synaptic actions on muscle fibers are mediated by one neurotransmitter, acetylcholine (ACh), which activates only one type of receptor (the ionotropic nicotinic ACh receptor); however, a single central neuron can respond to different types of inputs, each mediated by a distinct transmitter that alters the activity of specific types of receptor. These receptors include both ionotropic receptors, where binding of transmitter directly opens an ion channel, and metabotropic receptors, where transmitter binding indirectly regulates a channel by activating second messengers. As a result, unlike muscle fibers, central neurons must integrate diverse inputs into a single coordinated action. Finally, the nerve–muscle synapse is a model of efficiency—every action potential in the motor neuron produces an action potential in the muscle fiber. In comparison, connections made by a presynaptic neuron onto the motor neuron are only modestly effective—often 50 to 100 excitatory neurons must fire together to produce a synaptic potential large enough to trigger an action potential in a motor cell.

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The first insights into synaptic transmission in the ...

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